Therapeutic Potential of „Derived-Multiple Allogeneic Proteins Paracrine Signaling-D-Mapps” in the Treatment of Dry Eye Disease

Abstract

Dry eye disease (DED) is a chronic inflammatory disease of the lacrimal system and ocular surface. Considering the important role of inflammation in DED development, the main treatment strategy has shifted from hydration and lubrication of dry ocular surface to the immunomodulation and immunoregulationapproach that should address the main pathologic processes responsible for disease progression. Due to their capacity for production of immunosuppressive factors, mesenchymal stem cells (MSCs) and their secretome have been considered as potentially new agents in DED therapy. We recently developed an immunomodulatory ophthalmic solution “derived- Multiple Allogeneic Proteins Paracrine Signaling (d-MAPPS)” which activity is relied on immunosuppressive capacity of MSC-derived secretome. d-MAPPS contains MSC-derived exosomes, growth factors and immunosuppressive cytokines that are able to efficiently suppress generation of inflammatory phenotype in T cells and macrophages. Herewith, we demonstrated that d-MAPPS protected human corneal epithelial cells from chemical injury and efficiently alleviated ocular discomfort and pain in 131 DED patients during the 12-month follow-up, indicating d-MAPPS eye drops as potentially new remedy for the treatment of DED patients.

Therapeutic Potential of d-MAPPS™ for Ocular Inflammatory Diseases and Regeneration of Injured Corneal and Retinal Tissue

“…d-MAPPS™ improved survival and restored the morphology of benzalkonium chloride (BAK)-treated human corneal epithelial cells (HCECs) [ 13 ]. BAK is a quaternary ammonium compound which is widely used as a preservative in eye drops [ 17 ].…”

“…BAK alters the morphology of HCEC, modulates signaling pathways which regulate the HCEC cycle, affects the release of adenosine three phosphate (ATP), induces oxidative stress in HCECs, and induces direct cytotoxic effects by promoting the activation of caspase-3-dependent apoptosis in injured HCECs [ 17 ]. BAK-treated HCECs which grew under the presence of d-MAPPS™ restored their morphology and function [ 13 ]. Loss of cell-to-cell contact was not observed in BAK+ d-MAPPS™-treated HCECs which grew in the same manner as under standard culture conditions.…”

“…Loss of cell-to-cell contact was not observed in BAK+ d-MAPPS™-treated HCECs which grew in the same manner as under standard culture conditions. Importantly, d-MAPPS™ significantly improved the viability of BAK-injured HCEC and restored their protective and immunoregulatory functions [ 13 ]. As evidenced by scratch/wound healing assay (the most commonly used method for studying cell migration and proliferation patterns in vitro) [ 13 ], researchers from the University of Florida revealed that d-MAPPS™ significantly improved the migratory and proliferative properties of HCEC, resulting in the complete restoration of corneal wounds induced in vitro.…”

“…Importantly, d-MAPPS™ significantly improved the viability of BAK-injured HCEC and restored their protective and immunoregulatory functions [ 13 ]. As evidenced by scratch/wound healing assay (the most commonly used method for studying cell migration and proliferation patterns in vitro) [ 13 ], researchers from the University of Florida revealed that d-MAPPS™ significantly improved the migratory and proliferative properties of HCEC, resulting in the complete restoration of corneal wounds induced in vitro. Cell-to-cell contacts of HCECs were completely restored after 96 h of d-MAPPS™-based treatment [ 13 ], indicating the therapeutic potential of d-MAPPS™ in the treatment of corneal wounds ( Figure 1 ).…”

“…In line with these observations, we recently developed “derived- Multiple Allogeneic Proteins Paracrine Signaling d-MAPPS™ regenerative biologics platform technology”, which is a bioengineered biological product derived from human amniotic fluid (AF), manufactured under current Good Manufacturing Practices (cGMP), regulated and reviewed by the Food and Drug Administration (FDA) [ 11 ]. The therapeutic potential of d-MAPPS™ in the treatment of inflammatory eye diseases and in corneal regeneration has been documented in several in vitro studies and pilot clinical trials, indicating that it could be considered a new therapeutic agent in regenerative ophthalmology [ 11 , 12 , 13 , 14 , 15 , 16 ]. Herewith, we emphasized the molecular mechanisms responsible for the therapeutic efficacy of d-MAPPS™ and present the main beneficial effects of d-MAPPS™ which have been observed in clinical settings.…”